ArticleHuman mutation2015
Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome.
Article in Human mutation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Update on the Clinical and Molecular Characterization of Noonan Syndrome and Other RASopathies: A Retrospective Study and Systematic Review.International journal of molecular sciences · 2025Pooled it
- The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading.Molecular cancer therapeutics · 2024Article
- Review
- Immunological and hematological findings as major features in a patient with a new germline pathogenic CBL variant.American journal of medical genetics. Part A · 2024Article
- RASopathies - what they reveal about RAS/MAPK signaling in skeletal muscle development.Disease models & mechanisms · 2024Review
- Computer-based facial recognition as an assisting diagnostic tool to identify children with Noonan syndrome.BMC pediatrics · 2024Article
- Non-Mammalian Models for Understanding Neurological Defects in RASopathies.Biomedicines · 2024Review
- Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography.Journal of medicinal chemistry · 2024Article
- Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients.Archives of toxicology · 2023Article
- The molecular genetics of RASopathies: An update on novel disease genes and new disorders.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study.American journal of medical genetics. Part A · 2022Article
- Review
- Cognitive Phenotype and Psychopathology in Noonan Syndrome Spectrum Disorders through Various Ras/MAPK Pathway Associated Gene Variants.Journal of clinical medicine · 2022Article
- The RASopathies: from pathogenetics to therapeutics.Disease models & mechanisms · 2022Review
- Hypertrophic Cardiomyopathy in RASopathies: Diagnosis, Clinical Characteristics, Prognostic Implications, and Management.Heart failure clinics · 2022Review
- SOS2 Comes to the Fore: Differential Functionalities in Physiology and Pathology.International journal of molecular sciences · 2021Review
- Ras Isoforms from Lab Benches to Lives-What Are We Missing and How Far Are We?International journal of molecular sciences · 2021Review
- Drosophila RASopathy models identify disease subtype differences and biomarkers of drug efficacy.iScience · 2021Article
- Allosteric autoactivation of SOS and its kinetic mechanism.Small GTPases · 2021Article
- Anchorage-independent growth conditions reveal a differential SOS2 dependence for transformation and survival inSmall GTPases · 2021Article
Corrections and comments
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Authors and funding
39 authors at 20 institutions in 7 countries.
Funding
Abstract
The RASopathies constitute a family of autosomal-dominant disorders whose major features include facial dysmorphism, cardiac defects, reduced postnatal growth, variable cognitive deficits, ectodermal and skeletal anomalies, and susceptibility to certain malignancies. Noonan syndrome (NS), the commonest RASopathy, is genetically heterogeneous and caused by functional dysregulation of signal transducers and regulatory proteins with roles in the RAS/extracellular signal-regulated kinase (ERK) signal transduction pathway. Mutations in known disease genes account for approximately 80% of affected individuals. Here, we report that missense mutations altering Son of Sevenless, Drosophila, homolog 2 (SOS2), which encodes a RAS guanine nucleotide exchange factor, occur in a small percentage of subjects with NS. Four missense mutations were identified in five unrelated sporadic cases and families transmitting NS. Disease-causing mutations affected three conserved residues located in the Dbl homology (DH) domain, of which two are directly involved in the intramolecular binding network maintaining SOS2 in its autoinhibited conformation. All mutations were found to promote enhanced signaling from RAS to ERK. Similar to NS-causing SOS1 mutations, the phenotype associated with SOS2 defects is characterized by normal development and growth, as well as marked ectodermal involvement. Unlike SOS1 mutations, however, those in SOS2 are restricted to the DH domain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.